{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:29:51Z","timestamp":1790429391943,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3481,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1996,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective<\/jats:italic>. To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation. T cell receptor (TCR) \u03b2\u2010chain sequences were amplified by reverse transcriptase\u2013polymerase chain reaction, using TCR BV and BJ gene segment\u2013specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (<jats:italic>P<\/jats:italic> &lt; 0.0001) and in patients with psoriatic arthritis (<jats:italic>P<\/jats:italic> = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (<jats:italic>P<\/jats:italic> = 0.005 and <jats:italic>P<\/jats:italic> = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cell specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.<\/jats:p>","DOI":"10.1002\/art.1780390606","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T11:40:11Z","timestamp":1171453211000},"page":"904-913","source":"Crossref","is-referenced-by-count":98,"title":["Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings"],"prefix":"10.1002","volume":"39","author":[{"given":"Inge","family":"Waase","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Kayser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula 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